Is CFAP52 p.Leu251= (c.751T>C) pathogenic?

CFAP52 p.Leu251= (c.751T>C) is classified Likely benign in CFAP52 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-01). Ultra-rare (popmax 0.0164%, mid); Associated with situs inversus.

What condition is associated with CFAP52 p.Leu251= (c.751T>C)?

CFAP52 p.Leu251= (c.751T>C) is associated with situs inversus (ClinVar).

How common is CFAP52 p.Leu251= (c.751T>C) in the general population?

CFAP52 p.Leu251= (c.751T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CFAP52 p.Leu251=

c.751T>C · rs371814923 · VCV1453935

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

situs inversus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -3.7, phastCons 0.05
Overall
CADD	10.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00328% 53/1,613,474 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.00432%	23,129
Remaining individualsnot grpmax-eligible	0.0016%	62,460

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CFAP52
Protein: p.Leu251=
Coding: c.751T>C
MANE Select: NM_145054
dbSNP: rs371814923
Type: single nucleotide variant
Location: chr17:9600181 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 2 PDB

Full CFAP52 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

situs inversus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP52 p.Ala147Thr Uncertain significance ★★ ⚠ same condition
CFAP52 p.Ala161Asp Uncertain significance ★★ ⚠ same condition
CFAP52 p.Arg170Gln Uncertain significance ★★ ⚠ same condition
CFAP52 p.Arg594Cys Uncertain significance ★★ ⚠ same condition
CFAP52 p.Gly343Ser Uncertain significance ★★ ⚠ same condition
CFAP52 p.Gly534Ala Uncertain significance ★★ same condition
CFAP52 p.Met551Thr Uncertain significance ★★ ⚠ same condition
CFAP52 p.Tyr41His Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cfap52-p-leu251 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown